Hepatic intra-arterial delivery of a retroviral vector expressing the cytosine deaminase gene, controlled by the CEA promoter and intraperitoneal treatment with 5-fluorocytosine suppresses growth of colorectal liver metastases.
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Targeting of colorectal liver metastases by regional gene therapy was tested in a clinically relevant syngeneic model. First, the CEA-CD-113 retroviral vector containing the cytosine deaminase gene controlled by the CEA specific tumour cell promoter, was shown in vitro to convert 5-fluorocytosine to 5-fluorouracil, resulting in cancer cell killing with a large bystander effect. Second, 10 days after the establishment of liver metastases, retroviral vectors were delivered to the liver by hepatic artery injection. After 5-fluorocytosine administration for 7 days, most surface metastases disappeared and tumour volumes were suppressed up to 8.2-fold. The results support the development of this approach for patient treatment. (+info)
Reconstruction of double hepatic arterial and portal venous branches for right-lobe living donor liver transplantation.
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Double hepatic arterial and portal venous branches are common anatomic variations of the isolated right hepatic lobe. Reconstruction of these vessels during transplantation can be challenging because of their small caliber, close proximity to other hilar structures, and abnormal alignment with the native vasculature. Practical techniques for the creation of these anastomoses would simplify the recipient surgery and might minimize the incidence of vascular complications. Alternative methods for management of these structures are summarized. The recipient's proper hepatic artery and its bifurcation are resected for use as an arterial Y-type graft. The donor arteries are individually anastomosed at the bifurcation of the recipient's hepatic artery at the back table. The free end of the Y graft is then replaced at the origin of the gastroduodenal artery using standard branch-patch technique. Reconstruction of a second donor portal branch is similarly facilitated by ex situ placement of a Y-type vascular conduit derived from the recipient's portal vein. Surgical management of these vessels and reconstruction of other hilar structures are noticeably less cumbersome. There have been no short-term vascular complications. The use of autologous vascular conduits with ex situ reconstruction facilitates management of double donor arterial and portal venous branches. The incidence of complications attributable to these methods is expected to be low. (+info)
Accuracy and utility of 3-dimensional computed tomography in evaluating donors for adult living related liver transplants.
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Three-dimensional (3D) computed tomography (CT) is an imaging technique that renders anatomic detail in 3D images from helical computed tomographic scans. The purpose of this study is to assess 3D CT in the preoperative evaluation of adult living related liver transplant donors. Nine patients underwent right-lobe liver resection for adult living related liver transplants between October 1999 and September 2000. All donors underwent triphasic helical CT of the liver with 3D computed tomographic reconstruction and conventional angiography. The 3D images were correlated with angiography and intraoperative findings. The origin of vessels, relative length of segments, and position of branches were considered for accuracy. The 3D computed tomographic images were compared with angiograms to determine whether angiography could be replaced by 3D CT. 3D CT identified all variations of the hepatic vein confluences and portal vein trifurcations and all hepatic arterial variants. At surgery, the 3D computed tomographic images of hepatic and portal veins were judged to be accurate and helpful in 8 of 9 cases, and images of the hepatic artery, accurate and helpful in 5 of 9 cases. The 3D computed tomographic images of hepatic and portal veins were better than or equivalent to angiograms in nearly all cases. The 3D computed tomographic images of the hepatic artery were better than or equivalent to angiography in 5 of 9 cases. By providing an accurate 3D map of the liver and its vasculature, 3D computed tomographic reconstructions of the hepatic vasculature are a useful adjunct for surgical planning in adult living related liver donors. 3D CT clearly delineates portal and hepatic veins as well as or better than the angiogram and can identify the hepatic artery and its branches well enough to consider replacing angiography, thus reducing cost, inconvenience, and risk to the donor. (+info)
Review article: non-systemic chemotherapy in the treatment of colorectal cancer-portal vein, hepatic arterial and intraperitoneal approaches.
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Loco-regional chemotherapy, an alternative to systemic chemotherapy in the management of colorectal cancer, has been evaluated in both adjuvant and palliative settings. The rationale for loco-regional delivery is to achieve higher dose concentrations of drugs at the tumour site or at the most common sites of tumour recurrence, while limiting systemic exposure and associated toxicity. Adjuvant intraportal chemotherapy and palliative hepa-tic arterial chemotherapy have been most extensively investigated. Intraperitoneal chemotherapy has also been studied as an adjuvant treatment after complete resection of colorectal cancer or cytoreductive surgery in patients with established peritoneal carcinomatosis. The results obtained have been disappointing, and none of these procedures can be considered as a standard therapeutic option today. However, methodological difficulties were encountered in most published studies, and the investigated schedules and doses may not have been optimal. New combinations of cytotoxic drugs and new indications are currently under consideration. Promising results have recently been published for adjuvant intraperitoneal chemotherapy and hepatic arterial chemotherapy following surgical resection of hepatic metastases, but additional well-designed multicentre phase III trials are needed to determine the true benefits of these treatment modalities and to address the issues of cost and quality of life. (+info)
Therapeutic efficacy of transcatheter arterial embolization of primary hepatocellular carcinoma: discrepancy in different histopathologic subtypes.
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OBJECTIVE: To evaluate preliminarily the therapeutic efficacy of transcatheter arterial embolization (TAE) for different histopathologic subtypes of primary hepatocellular carcinoma (HCC). METHODS: A retrospective study of 226 patients with histopathologically diagnosed primary HCC was performed. The patients were treated with either single TAE, surgical resection of tumor alone, or TAE combined with surgical resection. Follow-up information was achieved in 157 of 226 patients. Comparative analyses of survival data and image findings were performed with correlation to histopathologic classification and different therapeutic methods, respectively. RESULTS: Eight histopathologic subtypes of primary HCC were found in this group, including HCC of trabecular pattern, pseudoglandular pattern, fibrolamellar HCC and sclerosing HCC, as well as HCC of clear cell, of small cell, poorly differentiated or undifferentiated HCC, and hormonally active HCC. The accumulated survival rate for these 157 patients was 74.52% of 1 year, 53.50% of 2 years, 31.85% and 14.01% of 3 and 5 years, respectively. Fibrolamellar HCC and clear cell HCC had relatively higher survival rate (25.00% and 33.22% of 5 years, respectively) than that of other subtypes, and the median survival time of the latter was 71 months. The mean survival time was 25.06 months (SE = 1.87) in single TAE group, 30.38 (SE = 2.05) months in surgical resection, and 72 months (SE = 6.90) in TAE combined with resection. CONCLUSIONS: Discrepancies do exist in therapeutic effect of different subtypes of HCC. In this study, clear cell HCC was more sensitive to TAE than other subtypes, and, in contrast, small cell HCC and poorly differentiated or undifferentiated HCC were of lower sensitivity to TAE. (+info)
Diagnosis and treatment of splanchnic artery aneurysms: a report of 57 cases.
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OBJECTIVE: To evaluate the diagnosis and treatment of splanchnic artery aneurysms. METHODS: A retrospective study of our case records from 1957 to 1997 was carried out. Fifty-seven patients with splanchnic artery aneurysms were involved in this study with 62 aneurysms, including hepatic aneurysm (14 patients), gastric and pancreaticoduodenal aneurysm (13), splenic aneurysm (14), renal aneurysm (6), superior mesenteric aneurysm (3), inferior mesenteric aneurysm (1), truncus coeliacus (3) and epiploic arterial aneurysm (3). Among them, 5 patients had multiple aneurysms; 29 had massive bleeding of spontaneous rupture into the biliary tract (14 patients), the upper gastrointestinal tract (10), and the peritoneal and retroperitoneal cavity (5). RESULTS: Preoperative diagnosis was confirmed by arteriography in 37 patients, digital subtraction angiography (DSA) in 2, and magnetic resonance angiography (MRA) in 2. Among the 46 patients who underwent surgical intervention, 9 died. Splanchnic arterial embolotherapy was performed in 6 patients. CONCLUSION: Splanchnic artery aneurysms have a potential for rupture with life-threatening hemorrhage. Clinical assessment of these lesions before operation is very difficult. The most valuable examination is selective arteriography of the splanchnic artery (including DSA). Surgical treatment is a safe and effective procedure. Embolic therapy may be the method of choice for selected splanchnic artery aneurysms. Prognosis of this disorder depends on the anatomic location of aneurysms, primary disease and general condition of patients. (+info)
Insulin and C-peptide secretion and kinetics in humans: direct and model-based measurements during OGTT.
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To directly evaluate prehepatic secretion of pancreatic hormones during a 3-h oral glucose tolerance test (OGTT), we measured insulin and C-peptide in six healthy control, six obese, and six type 2 diabetic subjects in the femoral artery and hepatic vein by means of the hepatic catheterization technique. Hypersecretion in obesity was confirmed (309 +/- 66 nmol in obese vs. 117 +/- 22 in control and 79 +/- 13 in diabetic subjects, P 0.3, r(2) = 0.93), whereas estimation of hepatic insulin extraction and insulin clearance needs further investigation for improvement. (+info)
Toxicology of intrahepatic arterial administration of interventional phosphorus-32 glass microspheres to domestic pigs.
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OBJECTIVE: To evaluate the toxic response to intrahepatic arterial administration of radioactive phosphorus-32 glass microspheres (32P-GMS) in domestic pigs. METHODS: Through selective catheterization of hepatic artery, 32P-GMS was infused to 5 healthy domestic pigs in a dosage equivalent to the therapeutic dose for human being, and 31P-GMS was infused to other 5 healthy domestic pigs. Two pigs served as the whole course blank controls. One pig from each group was surrendered to euthanasia at week 1, 2, 4, 8 and 16, respectively, and liver biopsies were performed on the rest of pigs at the corresponding time points. Liver tissues from different sites were taken for light and electron microscopy. The ultrastructural histopathological changes were evaluated semiquantitatively. RESULTS: The accumulative amount of 32P-GMS in the target tissue attained more than 90% of the total dose administrated. Histologically, abnormal hepatocytes were easily found at week 1 or 2. At week 4 they were less than at week 1 or 2, and endothelium of the sinuses were damaged prominently. At week 8 they were scarcely seen, and liver tissue recovered gradually. The histological features of liver tissue restored to normal at week 16. Semiquantitative analysis of ultrastructural morphology in the experimental group showed no statistical difference (P > 0.50) between the nuclear abnormality (Nabn) and mitochrondrial variability (Mvar) at week 1 or 2, but revealed prominent difference (P < 0.01, P < 0.001) as compared with those in other groups. In the experimental group the Nabn in tissues showed no significant difference (P > 0.20) between week 8 and week 16. CONCLUSION: 32P-GMS internal irradiation at the dosage equivalent to human therapeutic dosage exerts reversible injury to domestic pig liver tissue, and it takes more than 8 weeks for the injured liver tissue to recover. (+info)